566155-75-7Relevant articles and documents
Acridine-based agents with topoisomerase II activity inhibit pancreatic cancer cell proliferation and induce apoptosis
Goodell, John R.,Ougolkov, Andrei V.,Hiasa, Hiroshi,Kaur, Harneet,Remmel, Rory,Billadeau, Daniel D.,Ferguson, David M.
, p. 179 - 182 (2008)
A series of substituted 9-aminoacridines is evaluated for antiproliferative activity toward pancreatic cancer cells. The results indicate that the compounds inhibit cell proliferation by inducing a G1-S phase arrest. A model is also developed that explain
Design, synthesis and evaluation of ratiometric probes for hydrogencarbonate based on europium emission.
Bretonniere, Yann,Cann, Martin J,Parker, David,Slater, Rachel
, p. 1624 - 1632 (2004)
A series of cationic, zwitterionic and anionic macrocyclic europium complexes has been prepared incorporating a N or C- linked acridone chromophore that allows sensitisation of Eu emission following excitation at 390-410 nm. Each of these complexes select
Compound a preparation UNC1215 method
-
, (2017/03/14)
The invention discloses a method for preparing a compound UNC1215, belonging to the technical field of pharmaceutical chemistry synthesis. The method sequentially comprises the following steps: nitration, nitro reduction reaction, Buchwald reaction, esterolysis reaction, condensation reaction and the like. The overall reaction yield can reach 67%, which is higher than the yield (60%) in the document. The method changes the synthesis route, avoids the pipe sealing reaction, sequentially performs the nitration, reduction reaction, Buchwald reaction, hydrolysis reaction and condensation reaction, and is simple to operate.
Synthesis and evaluation of N-alkyl-9-aminoacridines with antibacterial activity
Benoit, Adam R.,Schiaffo, Charles,Salomon, Christine E.,Goodell, John R.,Hiasa, Hiroshi,Ferguson, David M.
, p. 3014 - 3017 (2014/06/24)
A series of 9-alkylaminoacridines were synthesized and evaluated for activity against two strains of methicillin-resistant and one strain of methicillin-sensitive Staphylococcus aureus. Results are presented that show a clear structure activity relationship between the N-alkyl chain length and antibacterial activity with peak MIC99 values of 2-3 μM for alkyl chains ranging from 10 to 14 carbons in length. Although prior work has linked the function of acridine-based compounds to intercalation and topoisomerase inhibition, the present results show that 9-alkylaminoacridines likely function as amphiphilic membrane-active disruptors potentially in a similar manner as quaternary ammonium antimicrobials.
Small-molecule ligands of methyl-lysine binding proteins: Optimization of selectivity for L3MBTL3
James, Lindsey I.,Korboukh, Victoria K.,Krichevsky, Liubov,Baughman, Brandi M.,Herold, J. Martin,Norris, Jacqueline L.,Jin, Jian,Kireev, Dmitri B.,Janzen, William P.,Arrowsmith, Cheryl H.,Frye, Stephen V.
supporting information, p. 7358 - 7371 (2013/10/21)
Lysine methylation is a key epigenetic mark, the dysregulation of which is linked to many diseases. Small-molecule antagonism of methyl-lysine (Kme) binding proteins that recognize such epigenetic marks can improve our understanding of these regulatory mechanisms and potentially validate Kme binding proteins as drug-discovery targets. We previously reported the discovery of 1 (UNC1215), the first potent and selective small-molecule chemical probe of a methyl-lysine reader protein, L3MBTL3, which antagonizes the mono- and dimethyl-lysine reading function of L3MBTL3. The design, synthesis, and structure-activity relationship studies that led to the discovery of 1 are described herein. These efforts established the requirements for potent L3MBTL3 binding and enabled the design of novel antagonists, such as compound 2 (UNC1679), that maintain in vitro and cellular potency with improved selectivity against other MBT-containing proteins. The antagonists described were also found to effectively interact with unlabeled endogenous L3MBTL3 in cells.
Synthesis and evaluation of 9-aminoacridines derived from benzyne click chemistry
Howell, Lesley A.,Howman, Aaron,O'Connell, Maria A.,Mueller, Anja,Searcey, Mark
scheme or table, p. 5880 - 5883 (2010/06/15)
A small set of 9-aminoacridine-3- and 4-carboxamides were synthesized efficiently using the benzyne/azide click chemistry. The products bind to duplex DNA but have different antitumour activity in the HL60 cell line.
Acridone-based inhibitors of inosine 5′-monophosphate dehydrogenase: Discovery and SAR leading to the identification of N-(2-(6-(4-ethylpiperazin-1- yl)pyridin-3-yl)propan-2-yl)-2-fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419)
Watterson, Scott H.,Chen, Ping,Zhao, Yufen,Gu, Henry H.,Dhar, T. G. Murali,Xiao, Zili,Ballentine, Shelley K.,Shen, Zhongqi,Fleener, Catherine A.,Rouleau, Katherine A.,Obermeier, Mary,Yang, Zheng,McIntyre, Kim W.,Shuster, David J.,Witmer, Mark,Dambach, Donna,Chao, Sam,Mathur, Arvind,Chen, Bang-Chi,Barrish, Joel C.,Robl, Jeffrey A.,Townsend, Robert,Iwanowicz, Edwin J.
, p. 3730 - 3742 (2008/02/12)
Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5′- monophosphate to xanthosine-5′-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical benefit of MMF is limited by what is generally believed to be compound-based, dose-limiting gastrointestinal (GI) toxicity that is related to its specific pharmacokinetic characteristics. Thus, development of an IMPDH inhibitor with a novel structure and a different pharmacokinetic profile may reduce the likelihood of GI toxicity and allow for increased efficacy. This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model.
Synthesis and evaluation of acridine- and acridone-based anti-herpes agents with topoisomerase activity
Goodell, John R.,Madhok, Avni A.,Hiasa, Hiroshi,Ferguson, David M.
, p. 5467 - 5480 (2007/10/03)
The discovery of new non-nucleoside antiviral compounds is of significant and growing interest for treating herpes virus infections due to the emergence of nucleoside-resistant strains. Using a whole cell virus-induced cytopathogenic assay, we tested a se
Identification of compounds with anti-West Nile virus activity
Goodell, John R.,Puig-Basagoiti, Francesc,Forshey, Brett M.,Shi, Pei-Yong,Ferguson, David M.
, p. 2127 - 2137 (2007/10/03)
The lack of antiviral compounds targeting flaviviruses represents a significant problem in the development of strategies for treating West Nile Virus (WNV), Dengue, and Yellow Fever infections. Using WNV high-throughput screening techniques developed in o
